Modern Strategies for Diagnosis and Treatment of Parasitic Diseases.

Parasites are very widely distributed in the environment and form complex relationships with their hosts, forming host-parasite systems [...].

Viruses of protozoan parasites and viral therapy: Is the time now right?

Infections caused by protozoan parasites burden the world with huge costs in terms of human and animal health. Most parasitic diseases caused by protozoans are neglected, particularly those associated with poverty and tropical countries, but the paucity of drug treatments and vaccines combined with increasing problems of drug resistance are becoming major concerns for their control and eradication. In this climate, the discovery/repurposing of new drugs and increasing effort in vaccine development should be supplemented with an exploration of new alternative/synergic treatment strategies. Viruses, either native or engineered, have been employed successfully as highly effective and selective therapeutic approaches to treat cancer (oncolytic viruses) and antibiotic-resistant bacterial diseases (phage therapy). Increasing evidence is accumulating that many protozoan, but also helminth, parasites harbour a range of different classes of viruses that are mostly absent from humans. Although some of these viruses appear to have no effect on their parasite hosts, others either have a clear direct negative impact on the parasite or may, in fact, contribute to the virulence of parasites for humans. This review will focus mainly on the viruses identified in protozoan parasites that are of medical importance. Inspired and informed by the experience gained from the application of oncolytic virus- and phage-therapy, rationally-driven strategies to employ these viruses successfully against parasitic diseases will be presented and discussed in the light of the current knowledge of the virus biology and the complex interplay between the viruses, the parasite hosts and the human host. We also highlight knowledge gaps that should be addressed to advance the potential of virotherapy against parasitic diseases.

CCR5 and CCR5Δ32 in bacterial and parasitic infections: Thinking chemokine receptors outside the HIV box.

The CCR5 molecule was reported in 1996 as the main HIV-1 co-receptor. In that same year, the CCR5Δ32 genetic variant was described as a strong protective factor against HIV-1 infection. These findings led to extensive research regarding the CCR5, culminating in critical scientific advances, such as the development of CCR5 inhibitors for the treatment of HIV infection. Recently, the research landscape surrounding CCR5 has begun to change. Different research groups have realized that, since CCR5 has such important effects in the chemokine system, it could also affect other different physiological systems. Therefore, the effect of reduced CCR5 expression due to the presence of the CCR5Δ32 variant began to be further studied. Several studies have investigated the role of CCR5 and the impacts of CCR5Δ32 on autoimmune and inflammatory diseases, various types of cancer, and viral diseases. However, the role of CCR5 in diseases caused by bacteria and parasites is still poorly understood. Therefore, the aim of this article is to review the role of CCR5 and the effects of CCR5Δ32 on bacterial (brucellosis, osteomyelitis, pneumonia, tuberculosis and infection by Chlamydia trachomatis) and parasitic infections (toxoplasmosis, leishmaniasis, Chagas disease and schistosomiasis). Basic information about each of these infections was also addressed. The neglected role of CCR5 in fungal disease and emerging studies regarding the action of CCR5 on regulatory T cells are briefly covered in this review. Considering the "renaissance of CCR5 research," this article is useful for updating researchers who develop studies involving CCR5 and CCR5Δ32 in different infectious diseases.

Parasitic infections of the spine: case series and review of the literature.

OBJECTIVEAlthough parasitic infections are endemic to parts of the developing world and are more common in areas with developing economies and poor sanitary conditions, rare cases may occur in developed regions of the world.METHODSArticles eligible for the authors' literature review were initially searched using PubMed with the phrases "parasitic infections" and "spine." After the authors developed a list of parasites associated with spinal cord infections from the initial search, they expanded it to include individual diagnoses, using search terms including "neurocysticercosis," "schistosomiasis," "echinococcosis," and "toxoplasmosis."RESULTSTwo recent cases of parasitic spinal infections from the authors' institution are included.CONCLUSIONSKey findings on imaging modalities, laboratory studies suggestive of parasitic infection, and most importantly a thorough patient history are required to correctly diagnose parasitic spinal infections.

Multifaceted roles of basophils in health and disease.

Until recently, basophils had often been neglected in immunologic studies because of their minority status among immune cells or confused with tissue-resident mast cells because of some phenotypic similarities between them in spite of different anatomic localization. It is now appreciated that basophils and mast cells are distinct cell lineages and that basophils play important and nonredundant roles distinct from those played by mast cells. On the one hand, basophils contribute beneficially to protective immunity, particularly against parasitic infections. On the other hand, basophils are involved in the development of various disorders, including allergy and autoimmune disease. Basophils interact with other immune cells and nonhematopoietic cells through cell-to-cell contact or basophil-derived factors, such as cytokines and proteases, contributing to the regulation of immune and allergic responses. In this review article we highlight recent advances in our understanding of basophil pathophysiology in human subjects and animal models by consolidating research findings reported during the past 5 years. Further studies on basophils and their products will help identify suitable targets for novel therapeutics in allergy and effective vaccines against parasitic infection.

Neurocysticercosis: mimics and chameleons.

Neurocysticercosis is the most common parasitic neurological disease worldwide, yet in Europe, it remains relatively uncommon, with many practitioners rarely seeing a case. However, immigration and international travel mean that it is becoming increasingly recognised and diagnosed in developed countries. Being a treatable condition, it is essential to be familiar with the diagnosis and to appreciate its mimics and breadth of its possible clinical presentations.

Gordon Wilson Lecture: Infectious Disease Causes of Cancer: Opportunities for Prevention and Treatment.

The role of infectious agents in cancer is generally underappreciated. However, approximately 20% of human cancers are caused by infectious agents and as such they rank second only to tobacco as a potentially preventable cause in humans. Specific viruses, parasites, and bacteria have been linked to specific human cancers. The infectious etiology for these specific cancers provides opportunities for prevention and treatment.

Vaccines to combat the neglected tropical diseases.

The neglected tropical diseases (NTDs) represent a group of parasitic and related infectious diseases such as amebiasis, Chagas disease, cysticercosis, echinococcosis, hookworm, leishmaniasis, and schistosomiasis. Together, these conditions are considered the most common infections in low- and middle-income countries, where they produce a level of global disability and human suffering equivalent to better known conditions such as human immunodeficiency virus/acquired immunodeficiency syndrome and malaria. Despite their global public health importance, progress on developing vaccines for NTD pathogens has lagged because of some key technical hurdles and the fact that these infections occur almost exclusively in the world's poorest people living below the World Bank poverty line. In the absence of financial incentives for new products, the multinational pharmaceutical companies have not embarked on substantive research and development programs for the neglected tropical disease vaccines. Here, we review the current status of scientific and technical progress in the development of new neglected tropical disease vaccines, highlighting the successes that have been achieved (cysticercosis and echinococcosis) and identifying the challenges and opportunities for development of new vaccines for NTDs. Also highlighted are the contributions being made by non-profit product development partnerships that are working to overcome some of the economic challenges in vaccine manufacture, clinical testing, and global access.

Operational modelling to guide implementation and scale-up of diagnostic tests within the health system: exploring opportunities for parasitic disease diagnostics based on example application for tuberculosis.

Research and innovation in the diagnosis of infectious and parasitic diseases has led to the development of several promising diagnostic tools, for example in malaria there is extensive literature concerning the use of rapid diagnostic tests. This means policymakers in many low and middle income countries need to make difficult decisions about which of the recommended tools and approaches to implement and scale-up. The test characteristics (e.g. sensitivity and specificity) of the tools alone are not a sufficient basis on which to make these decisions as policymakers need to also consider the best combination of tools, whether the new tools should complement or replace existing diagnostics and who should be tested. Diagnostic strategies need dovetailing to different epidemiology and structural resource constraints (e.g. existing diagnostic pathways, human resources and laboratory capacity). We propose operational modelling to assist with these complex decisions. Projections of patient, health system and cost impacts are essential and operational modelling of the relevant elements of the health system could provide these projections and support rational decisions. We demonstrate how the technique of operational modelling applied in the developing world to support decisions on diagnostics for tuberculosis, could in a parallel way, provide useful insights to support implementation of appropriate diagnostic innovations for parasitic diseases.

Stem cell therapy for the treatment of parasitic infections: is it far away?

Stem cell therapy is an interventional treatment that introduces new cells into damaged tissues, which help in treating many diseases and injuries. It has been proved that stem cell therapy is effective for the treatment of cancers, diabetes mellitus, Parkinson's disease, Huntington's disease, cardiovascular diseases, neurological disorders, and many other diseases. Recently, stem cell therapy has been introduced to treat parasitic infections. The culture supernatant of mesenchymal stem cells (MSCs) is found to inhibit activation and proliferation of macrophages induced by the soluble egg antigen of Schistosoma japonicum, and MSC treatment relieves S. japonicum-induced liver injury and fibrosis in mouse models. In addition, transplantation of MSCs into naïve mice is able to confer host resistance against malaria, and MSCs are reported to play an important role in host protective immune responses against malaria by modulating regulatory T cells. In mouse models of Chagas disease, bone marrow mononuclear cell has been shown effective in reducing inflammation and fibrosis in mice infected with Trypanosoma cruzi, and transplantation of the bone marrow mononuclear cells prevents and reverses the right ventricular dilatation induced by T. cruzi infection in mice. Preliminary clinical trials demonstrate that transplantation of bone marrow derived-cells may become an important therapeutic modality in the management of end-stage heart diseases associated with Chagas disease. Based on these exciting results, it is considered by stating that it is firmly believed that, within the next few years, we will be able to find the best animal models and the appropriate stem cell type, stem cell number, injection route, and disease state that will result in possible benefits for the patients with parasitic infections, and stem cell therapy, although at an initial stage currently, will become a real therapeutic option for parasitic diseases.

[Treatment of diseases acquired abroad]. / Behandlung von auf Fernreisen erworbenen Erkrankungen.

Most imported diseases can be well treated-provided the diagnosis is made in due time. For example, only the rapid and correctly performed treatment of falciparum malaria can impede severe complications and save the patient's life. Effective treatments for amebiasis, giardiasis, leishmaniasis and worm diseases are available. However, it has to be mentioned that evidence from clinical trials is often insufficient. Accordingly only few international guidelines for imported diseases exist.

Spinal infection: state of the art and management algorithm.

INTRODUCTION: Spinal infection is a rare pathology although a concerning rising incidence has been observed in recent years. This increase might reflect a progressively more susceptible population but also the availability of increased diagnostic accuracy. Yet, even with improved diagnosis tools and procedures, the delay in diagnosis remains an important issue. This review aims to highlight the importance of a methodological attitude towards accurate and prompt diagnosis using an algorithm to aid on spinal infection management. METHODS: Appropriate literature on spinal infection was selected using databases from the US National Library of Medicine and the National Institutes of Health. RESULTS: Literature reveals that histopathological analysis of infected tissues is a paramount for diagnosis and must be performed routinely. Antibiotic therapy is transversal to both conservative and surgical approaches and must be initiated after etiological diagnosis. Indications for surgical treatment include neurological deficits or sepsis, spine instability and/or deformity, presence of epidural abscess and upon failure of conservative treatment. CONCLUSIONS: A methodological assessment could lead to diagnosis effectiveness of spinal infection. Towards this, we present a management algorithm based on literature findings.

Severe pentastomiasis in children: a report of 2 cases.

Pentastomiasis is a type of parasitic zoonosis. Most patients with pentastomiasis are asymptomatic. We report here two pediatric patients with severe pentastomiasis (porocephaliais taiwan and armilliferiasis), and the results of their 6-year and 3-year follow-ups, respectively. The manifestations and outcomes of the two cases are described. The diagnoses were established by histopathologic and/or parasitologic examinations. After diagnosis, traditional Chinese medicine (TCM), as well as praziquantel and/or albendazole, were used for treatment. This report highlights the seriousness of pentastomiasis in children. We suggest TCM be considered as supplementary or even primary treatment of children with severe pentastomiasis.

The role of nutrition in integrated programs to control neglected tropical diseases.

There are strong and direct relationships between undernutrition and the disease caused by infectious organisms, including the diverse pathogens labeled as neglected tropical diseases (NTDs). Undernutrition increases the risk of infection, the severity of disease and the risk that children will die, while the physical damage, loss of appetite, and host responses during chronic infection can contribute substantially to undernutrition. These relationships are often synergistic. This opinion article examines the role of nutrition in controlling NTDs and makes the point that mass drug treatment--the major strategy currently proposed to control several diseases--is crucial to controlling disease and transmission, but is only the start of the process of physical recovery. Without adequate energy and nutrients to repair damaged tissues or recover lost growth and development, the benefits of treatment may not be evident quickly; the effects of control programs may be not appreciated by beneficiaries; while vulnerability to reinfection and disease may not be reduced. There is substantial potential for nutritional interventions to be added to large-scale programs to deliver drug treatments and thereby contribute, within a broad strategy of public health interventions and behavior change activities, to controlling and preventing NTDs in populations, and to restoring their health.

Cutaneous id reactions: a comprehensive review of clinical manifestations, epidemiology, etiology, and management.

Id reactions are a type of secondary inflammatory reaction that develops from a remote localized immunological insult. To date, id reactions caused by various fungal, bacterial, viral, and parasitic infections have been reported. Superficial fungal infections, especially tinea pedis, are the most common cause of id reactions. Id reactions exhibit multiple clinical presentations, including localized or widespread vesicular lesions, maculopapular or scarlatiniform eruptions, erythema nodosum, erythema multiforme, erythema annulare centrifugum, Sweet's syndrome, guttate psoriasis, and autoimmune bullous disease. The mechanisms underlying id reactions vary depending on the type of clinical presentation. The most important aspect of therapy involves the identification and adequate treatment of the underlying infection or dermatitis. This review comprehensively discusses the current state of the field concerning cutaneous id reactions, including diagnostic criteria, clinical presentations, underlying infectious conditions, etiologic agents, immunologic characteristics, histopathologic findings, and management strategies.

Leech infestation in children through body orifices: experience in a hospital in Bangladesh.

INTRODUCTION: Bangladesh harbors many leeches in its vast wetlands. Leeches have a tendency to enter through body orifices with potentially life-threatening consequences. Literature search revealed inadequate description of clinical manifestations and treatment of leech infestations in children. We describe our experience with leech infestations in children. METHODS: Between January 1, 2004 and December 31, 2010, 17 cases of leech infestation through body orifices in children were managed. This is a retrospective study on age, sex, route of leech entry, investigation and treatment, and outcome. RESULTS: Age ranged from 4.5 to 11 years (mean 6.4 ± 1.8) and females accounted for more than 70 %. The orifices of leech entry include urethra, vagina, and rectum. Leeches could be found in eight cases. Two boys with leeches in the urinary bladder needed suprapubic removal. Leeches were retrieved from the vagina under general anesthesia in three cases, and on three occasions leeches came out from the vagina after normal saline instillation. In nine cases with different routes of entry where leech was not found, instillation of normal saline was sufficient to stop bleeding. Fifteen cases presented with bleeding and transfusion was required in five cases with Hb% <7 gm/dl. CONCLUSIONS: Leech infestation through lower body orifices is common in children of rural Bangladesh. Prompt diagnosis is of paramount importance, and application of normal saline is effective in most cases. Sometimes surgical intervention is required.

Efficacy of Mesenchymal Stem Cells Therapy in Parasitic Infections: Are Anti-parasitic Drugs Combined with MSCs More Effective?

PURPOSE: Mesenchymal stem cells (MSCs) are mesodermal-origin postnatal stem cells that are able to self-renew and differentiate into several cell lineages. MSCs possess anti-inflammatory and anti-apoptotic activity, immunomodulatory action, as well as regenerative properties. Since MSCs also have antimicrobial properties, it has been suggested that they should be utilized for treating infectious diseases. In this study, the last pre-clinical advances in the efficacy of MSCs' therapy against parasitic diseases were reviewed. METHODS: Data about the effects of MSCs' therapy on experimental and pre-clinical parasitic infections were collected by searching relevant articles and reviewing them. RESULTS: In the present study, empirical findings on the impacts of MSCs' therapy against parasitic diseases were recapitulated. Studies have reported that the administration of MSCs reduces the burden of the parasite and modulates the levels of inflammatory and anti-inflammatory cytokines in parasitic diseases, including schistosomiasis, malaria, cystic echinococcosis, toxocariasis, leishmaniasis, and trypanosomiasis. Also, the administration of MSCs combined with anti-parasitic drugs enhanced anti-parasitic effects and immunomodulatory actions. CONCLUSION: Based on this review, empirical studies have revealed the beneficial effects of MSCs against some parasitic infections. This new therapeutic strategy showed both anti-parasitic and immunomodulatory effects. Also, the combination of anti-parasitic drugs with MSCs' therapy promoted anti-parasitic and immunomodulatory activities against parasitic infections.

Immunomodulatory Potential of Non-Classical HLA-G in Infections including COVID-19 and Parasitic Diseases.

Human Leukocyte Antigen-G (HLA-G), a polymorphic non-classical HLA (HLA-Ib) with immune-regulatory properties in cancers and infectious diseases, presents both membrane-bound and soluble (sHLA-G) isoforms. Polymorphism has implications in host responses to pathogen infections and in pathogenesis. Differential expression patterns of HLA-G/sHLA-G or its polymorphism seem to be related to different pathological conditions, potentially acting as a disease progression biomarker. Pathogen antigens might be involved in the regulation of both membrane-bound and sHLA-G levels and impact immune responses during co-infections. The upregulation of HLA-G in viral and bacterial infections induce tolerance to infection. Recently, sHLA-G was found useful to identify the prognosis of Coronavirus disease 2019 (COVID-19) among patients and it was observed that the high levels of sHLA-G are associated with worse prognosis. The use of pathogens, such as Plasmodium falciparum, as immune modulators for other infections could be extended for the modulation of membrane-bound HLA-G in COVID-19-infected tissues. Overall, such information might open new avenues concerning the effect of some pathogens such as parasites in decreasing the expression level of HLA-G to restrict pathogenesis in some infections or to influence the immune responses after vaccination among others.

Glycomarkers in parasitic infections and allergy.

Both helminth infections and contact with allergens result in development of a Th2 type of immune response in the affected individual. In this context, the hygiene hypothesis suggests that reduced prevalence of parasitic infections and successful vaccination strategies are causative for an increase of allergies in industrialized countries. It is therefore of interest to study glycans and their role as immunogenic structures in both parasitic infections and allergies. In the present paper we review information on the different types of glycan structure present in proteins from plant and animal food, insect venom and helminth parasites, and their role as diagnostic markers. In addition, the application of these glycan structures as immunomodulators in novel immunotherapeutic strategies is discussed.